Although cyclic 3',5'-adenosine monophosphate (cyclic AMP) appears to mediate many effects of both thyrotropin (TSH) and long-acting thyroid stimulator (LATS) on thyroid, the precise mechanism(s) by which TSH and LATS regulate thyroid function are not, as yet, clearly defined. Thus, recent studies in our laboratory suggest that prostaglandins play an important role in thyroid function and may be critical to the initial effects of both TSH and LATS. A primary objective of this study is to examine the effects and, where appropriate, the interrelationship of TSH, LATS, prostaglandins and cyclic AMP in thyroid in order to gain further insight into regulation of thyroid function in health and disease. There remains much uncertainty as to the pathogenetic role LATS plays in Graves' disease. In particular, the relationship of circulating LATS to clinical thyrotoxicosis and non-suppressible thyroid function is in some dispute. Investigation of this question and studies of the hypothalamic-pituitary-thyroid axis in (LATS-positive and LATS- negative) Graves' disease using thyrotropin-releasing hormone (TRH) have now become major clinical research objectives in our laboratory. Characterization of LATS as an immunoglobulin G (IgG) has raised the possibility that Graves' hyperthyroidism is an autoimmune disease and that LATS is an antibody to thyroidal antigen(s). However, the precise pathogenetic role of the immune response in Graves' disease is as yet unclear as is the relative influence of humoral and cellular immunity. A variety of methodologies are being used to further pursue the in vitro interaction between LATS-IgG and thyroid. In vitro studies with human lymphocyte cultures, isolated thyroid cells, and thyroid cell monolayers are being pursued in an attempt to dissociate the humoral and cellular aspects of the immune response in Graves' disease and Hashimoto's thyroiditis and to provide a better correlation between clinical severity of disease and intensity (or nature) of the immune response. Such an approach may ultimately lead to a more rational approach to treatment of Graves' hyperthyroidism.